Subscribe to RSS
DOI: 10.1055/a-1643-5729
Unified Approach to ent-Eudesmane-Type Terpenoid Synthesis: Total Synthesis of Sinupol and Eutyscoparin A
![](https://www.thieme-connect.de/media/synthesis/202203/lookinside/thumbnails/ss-2021-f0517-op_10-1055_a-1643-5729-1.jpg)
Abstract
ent-Eudesmane-type terpenoids constitute a large class of natural products derived from plants, animals, and bacteria. We describe a synthetic approach to two ent-eudesmane-type terpenoids, sinupol and eutyscoparin A, that relies on a key π-facial- and endo/exo-selective intramolecular Diels–Alder reaction to set the C-5–C-10 stereotriads. Further key transformations of trans-fused decalin include conversion to methyl ketone via a versatile thioester intermediate and appropriate functionalization toward target compounds.
Key words
ent-eudesmane - sinupol - eutyscoparin A - total synthesis - Diels–Alder reaction - protecting-group-freeSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-1643-5729.
- Supporting Information
Publication History
Received: 31 August 2021
Accepted after revision: 13 September 2021
Accepted Manuscript online:
13 September 2021
Article published online:
19 October 2021
© 2021. Thieme. All rights reserved
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References
- 1a Fraga BM. Nat. Prod. Rep. 2011; 28: 1580
- 1b Li W, Chen H.-Q, Wang H, Mei W.-L, Dai H.-F. Nat. Prod. Rep. 2021; 38: 528
- 1c Rudolf JD, Alsup TA, Xu B, Li Z. Nat. Prod. Rep. 2021; 38: 905
- 1d Zheng QX, Xu ZJ, Sun XF, Guéritte F, Cesario M, Sun HD, Cheng CH. K, Hao X.-J, Zhao Y. J. Nat. Prod. 2003; 66: 1078
- 1e Shen Y, Cui S.-J, Chen H, Shen L, Wang M, Dong X, Xiao C.-J, Jiang B. J. Nat. Prod. 2020; 83: 927
- 2 Wu Q.-X, Shi Y.-P, Jia Z.-J. Nat. Prod. Rep. 2006; 23: 699
- 3 Ando M, Isogai K, Azami H, Hirata N, Yanagi Y. J. Nat. Prod. 1991; 54: 1017
- 4a Tsanuo MK, Hassanali A, Jondiko IJ. O, Torto B. Phytochemistry 1993; 34: 665
- 4b Vera N, Misico R, Sierra MG, Asakawa Y, Bardón A. Phytochemistry 2008; 69: 1689
- 5a Al-Dabbas MM, Hashinaga F, Abdelgaleil SA. M, Suganuma T, Akiyama K, Hayashi H. J. Ethnopharmacol. 2005; 97: 237
- 5b Li W, Cai C.-H, Guo Z.-K, Wang H, Zuo W.-J, Dong W.-H, Mei W.-L, Dai H.-F. Fitoterapia 2015; 100: 44
- 6 Zhang J, Wang Y, Zhu R, Li Y, Li Y, Qiao Y, Zhou J, Lou H. RSC Adv. 2018; 8: 39091
- 7 Wang X, Peng X, Tang C, Zhou S, Ke C.-Q, Liu Y, Yao S, Ai J, Ye Y. J. Nat. Prod. 2021; 84: 1626
- 8 Zhang J.-Z, Qiao Y.-N, Lin L, Wang Y.-J, Li Y, Fei X, Zhou J.-C, Wang X, Fan P.-H, Lou H.-X. Planta Med. 2016; 82: 1128
- 9 Isaka M, Palasarn S, Lapanun S, Chanthaket R, Boonyuen N, Lumyong S. J. Nat. Prod. 2009; 72: 1720
- 10 Kanemasa T, Kagawa K. Japan Kokai Tokkyo Koho JP08198745, 1999
- 11 Ye F, Zhu Z.-D, Gu Y.-C, Li J, Zhu W.-L, Guo Y.-W. Mar. Drugs 2018; 16: 103
- 12a Kenner KA, Anyanwu E, Olefsky JM, Kusari J. J. Biol. Chem. 1996; 271: 19810
- 12b Chen H, Wertheimer SJ, Lin CH, Katz SL, Amrein KE, Burn P, Quon MJ. J. Biol. Chem. 1997; 272: 8026
- 12c Ahmad F, Li PM, Meyerovitch J, Goldstein BJ. J. Biol. Chem. 1995; 270: 20503
- 12d Chen H, Cong LN, Li Y, Yao ZJ, Wu L, Zhang ZY, Burke TR. Jr, Quon MJ. Biochemistry 1999; 38: 384
- 12e Walchli S, Curchod ML, Gobert RP, Arkinstall S, Hooft van Huijsduijnen R. J. Biol. Chem. 2000; 275: 9792
- 12f Panzhinskiy E, Ren J, Nair S. Curr. Med. Chem. 2013; 20: 2609
- 13 Ota K, Kamaike K, Miyaoka H. Synlett 2020; 31: 1007
- 14 Zhang W, Lu X, Huo L, Zhang S, Chen Y, Zou Z, Tan H. J. Nat. Prod. 2021; 84: 1715
- 15a Evans DA, Ennis MD, Mathre DJ. J. Am. Chem. Soc. 1982; 104: 1737
- 15b Bradbury RH, Revill JM, Rivett JE, Waterson D. Tetrahedron Lett. 1989; 30: 3845
- 15c Carter RG, Weldon DJ. Org. Lett. 2000; 2: 3913
- 15d Nazari A, Heravi MM, Zadsirjan V. J. Organomet. Chem. 2021; 932: 121629
- 16 Kriening S, Evagelou A, Claasen B, Baro A, Laschat S. Eur. J. Org. Chem. 2014; 6720
- 17 Yildizhan S, Schulz S. Synlett 2011; 2831
- 18 Aoyama Y, Araki Y, Konoike T. Synlett 2001; 1452
- 19 Miyazaki T, Han-ya Y, Tokuyama H, Fukuyama T. Synlett 2004; 477
- 20 Wiest JM, Conner ML, Brown MK. J. Am. Chem. Soc. 2018; 140: 15943
- 21 Toyota M, Yonehara Y, Horibe I, Minagawa K, Asakawa Y. Phytochemistry 1999; 52: 689
- 22 CCDC 2095167 contains the supplementary crystallographic data for compound 10. The data can be obtained free of charge from The Cambridge Crystallographic Data Center via www.ccdc.cam.ac.uk/structures
- 23 White JD, Carter RG, Sundermann KF. J. Org. Chem. 1999; 64: 684
- 24 Kosugi H, Yamabe O, Kato M. J. Chem. Soc., Perkin Trans. 1 1998; 217
- 25 Comparison of the 13C NMR spectra of synthetic 1 and natural sinupol11 showed a difference in the chemical shift for C-4. Since the signal of C-4 is close to the solvent signal, it seems reasonable to assume that this signal might have been overlooked (see also Supporting Information). Although we could not obtain the spectrum of sinupol reported by Guo et al.,11 we are confident that the reported chemical shift for C-4 is a typographical error, given that all the other 13C NMR chemical shifts of synthetic 1 and natural sinupol are essentially identical.
- 26 Ueda T, Konishi H, Manabe K. Org. Lett. 2012; 14: 5370